1. Field of the Invention PA1 X is an organic moiety containing an iodinated aromatic group and a hydrophilic group, said moiety having an iodine content within the range of from about 40 to 80 weight percent based on the molecular weight of X. PA1 (i) a condensation polymer such as a polyester, polyamide, polyurethane, polycarbonate, polyepoxide, polyether, a phenolformaldehyde polymer and equivalent condensation polymers; PA1 (ii) an addition polymer produced by the polymerization of one or more addition polymerizable monomers containing a polymerizable unsaturated double bond, e.g., vinyl monomers, including such addition polymers as poly(vinyl alcohol), poly(alkylmethacrylates), poly(alkylacrylates), and equivalent addition polymers; or PA1 (iii) a naturally occurring polymer, for example, a polysaccharide containing repeating glucose units such as starch, glycogen, cellulose, cellulosic derivatives, and equivalent naturally occuring polymers. PA1 X is as defined in formula I above; PA1 L represents one of the above-described linking groups, e.g. ester, ether, amide, thioester, carbonate, carbamate, sulfide and the like; and each of R.sup.1 to R.sup.6 which may be the same or different, represents hydrogen, an iodine-containing substituent, or a hydrophilic group-containing substituent, with the proviso that the iodine content of X is from about 40 to 80 percent (based on the molecular weight of X).
This invention relates to an x-ray contrast composition for oral or retrograde administration to a mammal comprising water-insoluble iodinated polymeric beads as the contrast producing agent in a pharmaceutically acceptable carrier comprising a cellulose derivative.
2. Reported Developments
Roentgenographic examination utilizing x-rays and computed tomography (hereinafter CT) scans of fractures and other conditions associated with the skeletal system is routinely practiced without the use of contrast agents. X-ray visualization of organs containing soft tissue, such as the gastrointestinal (hereinafter GI) tract, requires the use of contrast agents which attenuate x-ray radiation. D. P. Swanson et al in "Pharmaceuticals In Medical Imaging", 1990, MacMillan Publishing Company, provides an excellent background in medical imaging utilizing contrast agents and compositions therewith.
The desiderata for an ideal GI contrast agent includes: good toxicological profile; the ability to fill the entire bowel/lumen and evenly coat the gut mucosa so that the presence of the bowel is detectable when the lumen is not distended; palatability and nonirritation to the intestinal mucosa; and passing through the GI tract without producing artifacts or stimulating vigorous intestinal peristalsis.
The most widely used contrast agents for the visualization of the GI tract is barium sulfate administered as a suspension orally or rectally as an enema. (See for example, U.S. Pat. Nos. 2,659,690; 2,680,089; 3,216,900; 3,235,462; 4,038,379 and 4,120,946) Notwithstanding its relatively good contrast characteristics, negligible absorption from the GI tract following oral or rectal administration and speedy excretion from the body, barium sulfate has certain disadvantages. In the presence of intestinal fluids, it lacks homogeneity which can result in poor x-ray images. In the colon, when administered as an enema, it flocculates and forms irregular clumps with fecal matter. The prior art considers as a serious problem the difficulty in achieving uniform adherence, and coating of, the mucosa of the GI tract by the water insoluble barium sulfate to provide high quality x-ray photographs. As a result of inadequate adherence to, and non-uniform coating of the mucosa, the x-ray results are often inferior, misleading to the practitioner and the imaging process must be repeated. It has also been observed that the barium sulfate, and other solid inorganic particulate radiopaque agents tend to settle out in the patient after evacuation but before and during x-ray imaging, which again deleteriously affects the quality of the x-ray pictures.
These drawbacks were addressed by many investigators and their efforts resulted in great improvements over the years. The drawbacks of unevenly coating of the mucosa with an insufficiently adherence thereto proved to be rather difficult to solve. To that end, the use of certain polymer additives were proposed as illustrated hereunder.
U.S. Pat. No. 4,069,306 discloses an x-ray contrast preparation which is said to adhere to the walls of body cavities. The preparation comprises a finely divided water-insoluble inorganic x-ray contrast agent and minute particles of a hydrophilic polymer which is insoluble in water but is water-swellable. The body cavity is supplied with such preparation suspended in water. The x-ray contrast agent is present in admixture with and/or enclosed in and/or adhered to said minute polymer particles.
U.S. Pat. No. 4,120,946 discloses a pharmaceutical composition for barium opacification of the digestive tract, comprising colloidal barium sulfate and a polyacrylamide in an aqueous vehicle. The polyacrylamide forms a viscous solution at low concentration which makes it possible to maintain the barium sulfate in suspension and at the same time permit good adherence of the preparation to the walls of the organ which it is desired to x-ray.
U.S. Pat. No. 5,019,370 discloses a biodegradable radiographic contrast medium comprising biodegradable polymeric spheres which carry a radiographically opaque element, such as iodine, bromine, samarium and erbium. The contrast medium is provided either in a dry or liquid state and may be administered intravenously, orally and intra-arterially.
While these polymeric materials greatly enhance attachment of the contrast agent used therewith to the walls of organs for better visualization thereof, they do not provide a uniform coating thereon. As such, there is still a need for an improved x-ray imaging medium that uniformly coats the soft tissues subjected to diagnostic x-ray examination.
It has now been discovered that high quality x-ray results can be obtained by utilizing a formulation comprising water-insoluble iodinated polymeric beads in combination with a cellulose derivative.